This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The envelope gene products of HIV and SIV play a critical role in the virus life cycle by mediating virus attachment and entry into the CD4-bearing target cell and also play a role in viral pathogenesis by modulating the immune response of the host. Our current studies have provided new insights into the process of viral entry/membrane fusion and have provided evidence for potential interactions between the cytoplasmic domain of these viruses and components of the cell. These novel observations point the way to three broad areas of continued investigation, which we are pursuing, as follows: + characterizing the role of the tryptophan-rich membrane-proximal (TRMP) domain of gp41 in Env-mediated membrane fusion and glycoprotein incorporation into virus. + analyzing the topology and structural requirements of the gp41 membrane-spanning domain for virus assembly and entry. + determining the role of sequences within the cytoplasmic domain (CD) of HIV Env in intracellular transport, and viral pathogenesis.